Endocrine Abstracts (2006) 11 P414

Polymorphisms in insulin-like growth factor binding protein-1 (IGFBP-1) are associated with increased type-2 diabetes mellitus prevalence

AH Heald1, RH Stephens2, P McElduff4, K Kaushal2, JP New2, J Worthington3, WE Ollier3, N Pendleton5, M Horan5, A Payton5 & JM Gibson2

1Bishop Auckland General Hospital, Bishop Auckland, United Kingdom; 2Vascular Research Group, Hope Hospital, Salford, United Kingdom; 3Centre for Integrated Genomic Medical Research, Stopford Building, Manchester, United Kingdom; 4School of Epidemiology and Health Sciences, Stopford Building, Manchester, United Kingdom; 5Ageing and Cognition Research Group, Clinical Sciences Building, Hope Hospital, Salford, United Kingdom.

Introduction: Dysregulation of the Insulin-like Growth Factor (IGF) system and particularly IGF-I and IGF-binding protein 1 (IGFBP-1) has been implicated in the aetiopathogenesis of obesity, diabetes mellitus and such complications such as cardiovascular disease and nephropathy. However, relatively little is known about the genomics of the IGF system in health and disease.

Methods: Six single nucleotide polymorphisms (SNPs) were genotyped in the IGFBP1 gene, in a representative sample of 732 Type-2 Diabetes patients from the Salford Diabetes Register and 359 aging healthy controls without diabetes from the Dyne-Steele Aging in Cognition Cohort, also based in Salford. All SNP’s were genotyped using ABI Taqman endpoint PCR.

Results: Two of these SNPs, T2877C in the second intron and A5881G in the 3′ flanking region, were associated with 2.6-fold and 2.7-fold increased prevalence of Type-2 Diabetes, respectively. The effect of these SNPs on odds ratios was not additive, and they were not in linkage dysequilibrium, suggesting independent association with disease risk. No functional effect of either SNP could be postulated from the data available.

Conclusion: These are the first genetic markers for Type-2 Diabetes prevalence described in IGFBP1. Our findings suggest that important genetic polymorphisms within the IGFBP1 gene, which may be in LD with those described here, exert important biological effects and remain to be characterised.